The development of novel routes to stereochemically and structurally complex targets of biological interest remains of paramount importance. New strategies, bond disconnections, and catalysts that exploit standard functional groups in innovative ways each contribute to the overall goal of increased scope and efficiency, and decreased time and cost. Catalysis, the use of substoichiometric amounts of reagent, without the need for covalent attachment or pretreatment, carries with it the promise of greener, more efficient, more selective methods for synthesis. This proposal seeks to develop novel methods to use traditional functional groups in non-traditional ways, accessing hitherto unavailable bond disconnection strategies in an effort to greatly expand our toolkit. In the context of this researc, we will apply these strategies to the formation of lactams, common structural features across many families of biologically active molecules. The specific goals of this research are as follows: 1) Develop asymmetric intermolecular Stetter reactions involving less activated Michael acceptors; 2) Control stereochemistry at the beta position via the homoenolate reactivity pathway; 3) Investigate oxidative pathways of enal activation; 4) Control oxidatively initiated [3+2]-type annulation of enals leading to cyclopentanone products. The long-term impact of this science is to enable chemists to rapidly assemble complex structures with high efficiency.